POS1507 IC3B/C3 RATIOS MORE STRONGLY CORRELATE WITH SLE DISEASE ACTIVITY IN AFRICAN-AMERICANS COMPARED WITH WHITES
Authors: D. Sen, V. Strand, Q. Fu, A. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Complement activation is a hallmark of SLE pathophysiology. We previously found that iC3b/C3 ratios associated with active disease and clinically meaningful changes in SLE disease activity. Since SLE is more severe in nonwhite populations, we hypothesized that iC3b/C3 ratios would be a more sensitive marker of disease activity in nonwhite populations. <h3>Objectives</h3> We examined the relationship of iC3b/C3 ratios between African-American (AA) and White subjects with classified SLE. <h3>Methods</h3> 159 adult SLE patients treated at the Washington University Lupus Center were enrolled in this observational study. 83 patients with 3-7 study visits were used for this longitudinal analysis. C3 and C4 were measured by nephelometry; iC3b by a lateral flow assay using an investigational medical device. SLE disease activity was measured using the SLEDAI 2K Responder Index-50 instrument. Statistical analyses were performed using SAS v9.4. Multilevel regression models examined associations for SLE disease activity. Ordinal logistic regression models with generalized estimating equation modeling (GEE) examined associations for clinically meaningful changes since the outcome variable is ordinal. Odds ratios and 95% confidence intervals were estimated using Proc GLIMMIX and Proc GENMOD. <h3>Results</h3> iC3b/C3 ratios and C3 associated with active disease in AA and White SLE subjects, with the association of the iC3b/C3 ratio in AA was stronger (Figure 1). In addition, AA with SLE associated C4, ESR, and dsDNA with active disease, while Whites associated with CRP. In multiple regression analysis, iC3b/C3 ratios independently associated with active disease in both groups, although the effect was more pronounced in AA (AA: OR=1.48, 95% CI=1.21-1.82; Whites: OR=1.17, 95% CI=1.02-1.34). Furthermore, in univariate regression analysis, only the iC3b/C3 ratio in AA associated with clinically meaningful changes in disease activity. <h3>Conclusion</h3> iC3/C3 ratios better correlated with active disease in AA compared to Whites. Furthermore, iC3b/C3 ratios correlated with clinically meaningful changes in disease activity only in AA. These data suggest that complement activation in SLE is dependent on race. <h3>Reference</h3> [1] Kim et al, Arthritis Rheumatol, 71:420, 2019, doi: 10.1002/art.40747 <h3>Acknowledgements</h3> I have no acknowledgements to declare.This research was funded/supported by Kypha, Inc. and National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R21AR069833. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. <h3>Disclosure of Interests</h3> Deepali Sen: None declared, Vibeke Strand Consultant of: AbbVie, Amgen, Arena Pharmaceuticals, Aria Pharmaceuticals, AstraZeneca, Bayer, Bristol Myers Squibb, Bioventus, Boehringer Ingelheim, Celltrion, ChemoCentryx, EMD Serono, Endo, Equillium, Galapagos, Genentech/Roche, Gilead Sciences, GSK, Horizon, Ichnos Sciences, Inmedix, Janssen, Kiniksa Pharmaceuticals, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Regeneron, Rheos Medicines, R-Pharm US, Samsung, Sandoz, Sanofi, Scipher Medicine, Servier Pharmaceuticals, SetPoint Medical, Sorrento Therapeutics, Sun Pharma, UCB., Qiang Fu: None declared, Alfred Kim Speakers bureau: AstraZeneca, Aurinia, Exagen Diagnostics, GlaxoSmithKline, Consultant of: Alexion, ANI Pharmaceuticals, AstraZeneca, Aurinia, Exagen Diagnostics, GlaxoSmithKline, Kypha, Pfizer, Grant/research support from: GlaxoSmithKline.